Vitamin D and Polycystic Ovarian Syndrome (PCOS)

Efficacy of Vitamin D Supplementation and Metformin Compared to Metformin Alone for Improvement in Follicle Size of Infertile Females With Polycystic Ovary Syndrome: a Randomized Open Label Trial

Primary Objectives:

To evaluate the efficacy of metformin and Vitamin D supplementation on serum insulin and serum androgen levels (Total testosterone, Steroid Hormone Binding Globulin, Free Androgen Index) levels compared metformin alone in infertile Poly cystic ovarian females of reproductive age group.

Secondary Objectives:

To measure change in endometrial thickness/number of follicles and follicular size by day 12 trans-vaginal ultrasound in the intervention group i.e. combination of metformin and vitamin D supplementation

Study Overview

• Status: Recruiting
• Conditions: Infertility; Vitamin D Deficiency; Infertility, Female
• Intervention / Treatment: Drug: Vitamin D

Detailed Description

Polycystic ovary syndrome (PCOS) as defined by "the presence of any two out of three criteria i.e. Oligo and/or anovulation, excess androgen activity and/or polycystic ovarian morphology on ultrasound", is a prevalent cause of female infertility. In the endocrine milieu of PCOS higher levels of insulin due to insulin resistance (IR) exert direct effects on the ovaries, release insulin-like growth factor 1 (IGF-1) from the liver and both then increase levels of testosterone. The resultant prevents the growth of ovarian follicles to acquire the required dimension for ovulation (i.e. > 10 mm) hence leading to anovulation and therefore subfertility. Vitamin D (VD) has found to be predominantly deficient in PCOS females, documented to cause IR giving rise to anovulatory cycles, hyperandrogenism and other significant features of PCOS. Therefore, we have hypothesized that treatment with VD in PCOS females can reduce IR, improve ovulation and signs of hyperandrogenism. Since Metformin is frequently prescribed for reducing IR and hence the treatment for anovulatory infertility in these females, we have planned to conduct an open label randomized control trial in PCOS infertile females who have vitamin D levels < than 25 ng/ml and are receiving Metformin therapy after ethical approval from Aga Khan University. The intervention group will receive VD Cholecalciferol (D2) 50,000 I.U once weekly for 12 weeks, followed by 50,000 I.U once every fortnight for 24 weeks with the Metformin treatment as prescribed by the physician whereas control group will receive Metformin treatment during the study period. We will compare change in number of dominant follicles (more than 10 mm) / endometrial thickness in both groups by Day 12 trans-vaginal ultrasound at the time of enrollment with scans done after 12 and 24 weeks. The other biochemical parameters [Total Testosterone, Steroid Hormone Binding Globulin, Free Androgen Index, Lipid Accumulation Product, Serum Insulin, Serum Triglycerides, Serum Calcium and Albumin] will be done at the time of recruitment in both the intervention and control groups and compared.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rehana K Rehman, PhD; Phone Number: 4460 00922134864460; Email: drrehana7@gmail.com

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 74800
      • Recruiting
      • Dr Rehana Rehman
      • Contact: Rehana Rehman; Phone Number: 03072227775; Email: rehana.rehman@aku.edu
      • Contact: Arfa Azhar; Phone Number: 4473 00922134864473; Email: arfa.azhar@aku.edu
    • Karachi, Sindh, Pakistan, 75500
      • Recruiting
      • Dr Rehana Rehman
      • Contact: Rehana Rehman; Phone Number: 03072227775; Email: rehana.rehman@aku.edu
      • Contact: Arfa Azhar; Phone Number: 4473 00922134864473; Email: arfa.azhar@aku.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 36 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Females with age range 18- 36 years, from all ethnic background having primary infertility with diagnosis of PCOS when at least 2 of these 3 elements are present: hyperandrogenism, chronic anovulation and polycystic ovaries and Vitamin D deficiency serum levels < 25 nmol/L

Exclusion Criteria:

exclusion criteria at baseline will be excluded from the study

• Females with secondary Infertility
• Hypercalcemia (plasma calcium concentrations> 2.65 mmol/L)
• Exclude women with Tuberculosis or other granulomatous disorders.
• Women receiving vitamin D replacement, oral contraceptives, hormonal replacement therapy, glucocorticoids, calcium supplementation, insulin-sensitizing drugs(incretin mimetic drugs, thiazolidinedione, sulfonylurea), lipid-lowering drugs or other drugs affecting insulin sensitivity or serum androgens (e.g., niacin, corticosteroids, beta-blockers, calcium channel blockers, thiazide diuretics), anti-epileptics, anti-retroviral, cholestyramine, anti-fungal, statins, H2 blockers, immunosuppressants, chemotherapeutic agents, antimicrobials (Rifampicin, isoniazid, hydroqychloroquin) or any other drug modifying lipid metabolism in the previous 3 months prior to study
• Women with congenital adrenal hyperplasia, Cushing's syndrome, androgen-secreting tumors, type 2 diabetes mellitus, renal, hepatic or thyroid disorders, hyperparathyroidism, malabsorption syndromes, Chronic Kidney Disease Hepatic failure, cystic fibrosis, vaginal bleeding of unknown etiology Women Those who had Bariatric surgery will also be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; control group will receive Metformin treatment during the study period.
Experimental: Vitamin D supplement; The intervention group will receive VD Cholecalciferol (D2) 50,000 I.U once weekly for 12 weeks, followed by 50,000 I.U once every fortnight for 24 weeks with the Metformin treatment as prescribed by the physician whereas	Drug: Vitamin D; Vitamin D supplementation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Insulin levels	Decrease in insulin levels 60%	24 weeks
• serum androgen levels	Decrease in Serum Androgen levels	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial thickness	increase in endometrial thickness to 2mm	24 weeks
Lipid Accumulation Product	reduction in lipid accumulation product	24 weeks

Collaborators and Investigators

• Sponsor: Aga Khan University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): June 13, 2025

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 17, 2019
• First Posted (Actual): June 18, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Infertility; Vitamin D Deficiency; Infertility, Female; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: 124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No